Integrated Molecular Characterization of Testicular Germ Cell Tumors | Zendy

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Integrated Molecular Characterization of Testicular Germ Cell Tumors

Author(s) -

Hui Shen,

Juliann Shih,

Daniel P. Hollern,

Linghua Wang,

Reanne Bowlby,

Satish K. Tickoo,

Vésteinn Thórsson,

Andrew J. Mungall,

Yulia Newton,

Apurva M. Hegde,

Joshua Armenia,

Francisco Sánchez-Vega,

John Pluta,

Louise C. Pyle,

Rohit Mehra,

Victor E. Reuter,

Guilherme Godoy,

Jeffrey Jones,

Carl Simon Shelley,

Darren R. Feldman,

Daniel Onofre Vidal,

Davor Lessel,

Tomislav Kuliš,

Flavio Mavignier Cárcano,

Kristen Leraas,

Tara M. Lichtenberg,

Denise Brooks,

Andrew D. Cherniack,

Juok Cho,

David I. Heiman,

L. Sylvia,

Minwei Liu,

Michael S. Noble,

Xi Liu,

Hailei Zhang,

Wanding Zhou,

Jean C. Zenklusen,

Carolyn M. Hutter,

Ina Felau,

Jiashan Zhang,

Nikolaus Schultz,

Gad Getz,

Matthew Meyerson,

Joshua M. Stuart,

Rehan Akbani,

David A. Wheeler,

Peter W. Laird,

Katherine L. Nathanson,

Victoria K. Cortessis,

Katherine A. Hoadley,

Daniel Hughes,

Kyle R. Covington,

Joy C. Jayaseelan,

Viktoriya Korchina,

Lora Lewis,

Hai Hu,

HarshaVardhan Doddapaneni,

Donna M. Muzny,

Richard A. Gibbs,

Benjamin G. Vincent,

Shengjie Chai,

Christof C. Smith,

J. Todd Auman,

Yan Shi,

Shaowu Meng,

Tara Skelly,

Donghui Tan,

Umadevi Veluvolu,

Piotr A. Mieczkowski,

Corbin D. Jones,

Matthew D. Wilkerson,

Saianand Balu,

Tom Bodenheimer,

Alan P. Hoyle,

Lisle E. Mose,

Janae V. Simons,

Matthew G. Soloway,

Jeffrey Roach,

Joel S. Parker,

D. Neil Hayes,

Charles M. Perou,

Gordon Saksena,

Carrie Cibulskis,

Steven E. Schumacher,

Rameen Beroukhim,

Stacey Gabriel,

Adrian Ally,

Miruna Balasundaram,

Rebecca Carlsen,

Dorothy Cheung,

Eric Chuah,

Noreen Dhalla,

Robert A. Holt,

Steven J.M. Jones,

Yussanne Ma,

Michael Mayo,

Richard A. Moore,

A. Gordon Robertson,

Jacqueline E. Schein,

Payal Sipahimalani,

Angela Tam,

Nina Thiessen,

Tina Wong,

Marco A. Marra,

Daniel J. Weisenberger,

David Van Den Berg,

Phillip H. Lai,

Mario Berríos,

Andrea Holbrook,

Arnoud Boot,

Dennis T. Maglinte,

Debyani Chakravarty,

Jianjiong Gao,

Zachary Heins,

Ritika Kundra,

Angelica Ochoa,

Chris Sander,

Marc Ladanyi,

Amie Radenbaugh,

Nils Gehlenborg,

Doug Voet,

Pei Lin,

Scott Frazer,

Seungchan Kim,

Michael S. Lawrence,

Thomas J. Giordano,

Timothy Defreitas,

Lynda Chin,

John N. Weinstein,

Wenbin Liu,

Gordon B. Mills,

Yiling Lu,

Leendert H. J. Looijenga,

Alan H. Bryce,

André Lopes Carvalho,

Michael Ittmann,

Seth P. Lerner,

Jay Bowen,

Julie M. GastierFoster,

Mark Gerken,

Carmen Helsel,

Nilsa C. Ramirez,

Lisa Wise,

Erik Zmuda,

Sandra Cottingham,

David Chesla,

Charles Saller,

Katherine Tarvin,

Luiz Fernando Lopes,

Cristovam ScapulatempoNeto,

Natália D. Aredes,

Wolter Oosterhuis,

Ad Gillis,

Hans Stoop,

W M H Eijkenboom,

George Sandusky,

Sue Martin,

Manju Aron,

Siamak Daneshmand,

Hooman Djaladat,

David I. Quinn,

Tanya B. Dorff,

Jochen K. Lennerz,

Leigh B. Thorne,

Marija Gamulin,

Željko Kaštelan,

Tvrtko Hudolin,

Christian Kubisch,

Lori Boice,

Mei Huang,

Amy H. Perou,

W. Kimryn Rathmell,

Todd Pihl,

Yunhu Wan,

Qiang Sun,

Rashi Naresh,

Sudha Chudamani,

Jia Liu,

Laxmi Lolla,

Ye Wu,

Martin L. Ferguson,

Margi Sheth,

John A. Demchok,

Liming Yang,

Roy Tarnuzzer,

Heidi J. Sofia,

Tanja M. Davidsen

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.05.039

Subject(s) - germ cell , biology , germ cell tumors , germ , computational biology , microbiology and biotechnology , cancer research , genetics , gene , chemotherapy

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.

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